ABSTRACT The transition through adolescence is characterized by a striking increase in symptoms and rates of depression. In fact, the majority of first episodes of MDD occur during adolescence. One-quarter of adolescents experience an episode of Major Depressive Disorder (MDD) by the end of their teenage years, and almost half of adolescents with a depressive episode experience a recurrence within three years. In attempting to identify factors that contribute to this high prevalence of depression in adolescence, investigators have focused on the adverse effects of exposure to stress occurring during childhood, or early life stress (ELS). ELS, including abuse, neglect, parental loss, and interpersonal stress, is associated with a marked increase in risk for subsequent depression. We do not yet understand, however, the mechanisms by which ELS contributes to this risk, thus hampering effective prevention and intervention efforts with adolescents. The proposed project is designed to examine trajectories of two psychobiological mechanisms that may explain how ELS increases risk for depression during adolescence: increased stress reactivity and blunted reward sensitivity. This focus on the trajectories of stress and reward systems is particularly salient in adolescence given that both of these systems undergo significant change and reorganization during this sensitive period of development. We propose to follow longitudinally 220 boys and girls who have already completed two comprehensive assessments (beginning at 9 to 12 years of age), two years apart, of their exposure to ELS, psychobiological functioning (including behavioral, cognitive, endocrine, and neural assessments of stress reactivity and reward sensitivity), and MDD symptoms and diagnosis. We will leverage data obtained from this large and richly-characterized sample of children to examine prospectively the developmental mechanisms by which ELS affects the onset and course of depression during adolescence. Specifically, we will integrate data from the participants? first two assessments completed in late childhood and early adolescence with new data that we propose to obtain at two additional assessments conducted in mid and late adolescence, a developmental period during which the incidence of MDD peaks. Specifically, we will continue to assess clinical characteristics, information-processing biases, endocrine functioning, and brain function, structure, and connectivity. Collectively, this approach will allow us to analyze the effects of ELS on trajectories of psychobiological and clinical functioning from childhood through late adolescence, and on deviations from normative trajectories of these constructs. Findings from this project will inform efforts to generate personalized targets in order to tailor prevention and treatment programs to adolescents who have been exposed to ELS and who, consequently, are at high risk for developing MDD.